Enzyme secretion, control

Q10 What factors normally control pancreatic enzyme secretion ... 

The bile canaliculus is formed as a bile capillary by means of a groove-like canal in the intercellular space, bounded by 2 adjacent liver cells. The bile canaliculi have no walls of their own, but are surrounded by a special zone of the cell membrane (so-calledpericanalicular ectoplasm). Their diameter amounts to 0.5-1.0 pm. They are interconnected and form an extensive polygonal network. The surface area of the bile capillaries is increased by microvilli, which show great functionally determined variability. The canalicular membrane constitutes 10% of the total plasma membrane in the hepatocytes. Similar to the pericanalicular ectoplasm, the hepatocytes contain contractile microfilaments and other components of the cytoskel-eton. These canaliculi are supplied with carrier proteins and enzymes to control bile secretion. (2,34)... 

Folsch, U. R., Cantor, P, Wilms, H, N Schafmayer, A ESecker, H., and Creutzfeldt, W, (1987). Role of cholecystokinin in the negative feedback control of pancreatic enzyme secretion in conscious rats. CasSroenifrohgy 92,449 58. 

As a result of proteolytic enzyme secretion into the duodenum, protein or peptide drugs, such as corticotropin, vasopressin, and insulin, are rapidly degraded and generally cannot be given orally. Secretory activity of the pancreas is under hormonal and neuronal control. 

Legraverend, C., A. Mode, T. Wells, I. Robinson, and J.A. Gustafsson (1992). Hepatic steroid hydroxylating enzymes are controlled by the sexually dimorphic pattern of growth hormone secretion in normal and dwarf rats. FASEB J. 6, 711-718. 

The mechanism by which surfactants increase enzyme secretion is not known. It seems likely that the leakiness of cell membranes may vary from one organism to another and thus account for the variability between strains in the amount of enzyme normally secreted. Surfactants may be expected to accumulate at the cell membrane and thereby further increase (or modify) leakiness. As the amount of cell-bound enzyme appears to remain constant (feed-back control), increased secretion leads to increased enzyme production as the cell attempts to maintain the cell-bound level. In the case of surfactant-stimulated production of a-amylase by A. oryzae, the higher enzyme production may be accompanied by a lower mycelial weight. At some critical level of surfactant, the effect on the cell wall becomes so great that the cells lyse, and growth as well as enzyme production cease. 

The levels of a-D-mannosidase activity in skin fibroblasts from cases of cystic fibrosis and controls have been compared. The effects of pH, metal ions, and heat have been studied on a-D-mannosidase from normal and mannosidosis fibroblasts and in culture medium derived from these. The results showed that enzymes secreted from mannosidosis fibroblasts behaved identically to the enzymes present in culture medium from normal fibroblasts. The implication of this finding was discussed. Two acidic forms of a-D-mannosidase activity, A and B have been separated and characterized from fibroblasts from controls and patients with mannosidosis. In normal cells, A and B differ in adsorption on DEAE-cellulose, electrophoretic mobility, stability at 70 °C, and resistance to freezing at — 20 °C, In five of six mutant cell lines, A and B both exhibited altered K s for artificial substrates, and decreased thermal stability. Zn had no effect on A or B in mutant or normal cells. In contrast, Co + slightly inhibited B in normal cells but markedly enhanced the activity of B in mutant cells. It was concluded that the mutation in mannosidosis results... 

We saw in Chapter 6 how the reserves in the endosperm of cereals are mobilized largely as a result of the activity of enzymes secreted by the aleurone layer. We also referred to the stimulation of aleurone layer activity by gibberellin coming from the embryo. Herein lies the basis of the control exerted by the embryo over food mobilization, which we will now examine more closely. 

The volume of extracellular fluid is direcdy related to the Na" concentration which is closely controlled by the kidneys. Homeostatic control of Na" concentration depends on the hormone aldosterone. The kidney secretes a proteolytic enzyme, rennin, which is essential in the first of a series of reactions leading to aldosterone. In response to a decrease in plasma volume and Na" concentration, the secretion of rennin stimulates the production of aldosterone resulting in increased sodium retention and increased volume of extracellular fluid (51,55). 

The enzymatic activity of these potentially harmful enzymes is tightly controlled. Once transcribed into protein, MMPs are expressed as inactive zymogens and require distinct activation processes to convert them into active enzymes. After secretion, MMP-activity is regulated by the noncovalent binding of tissue inhibitors of metalloproteinases ( TIMPs) as shown in Fig. 2 for MMP-2 and TIMP-2. Four TIMPs have been identified so far TIMP-1, TIMP-2, TIMP-3, and TIMP-4. All known MMPs can be inhibited by at least one of the four known TIMPs. Nevertheless, individual differences with regard to bond strength and thus the magnitude of inhibition of a particular MMP do exist. 

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